W2 Strain Of Plasmodium Falciparum Research Articles

Anthraquinones from the fruits of Vismia laurentii

Phytochemical study of the fruits of Vismia laurentii resulted in the isolation of five structurally related compounds. Three of them are constituents, namely, laurentiquinone A ( 1) (methyl 1,6,8-trihydroxy-3-methyl-7-(3-methylbut-2-enyl)-9,10-dioxo-9,10-dihydroanthracene-2-carboxylate), laurentiquinone B ( 2) (methyl 5,7-dihydroxy-2,2,9-trimethyl-6,11-dioxo-6,11-dihydro-2 H-anthra[2,3- b]pyran-8-carboxylate) and laurentiquinone C ( 3) (methyl 9-(ethanoyloxymethyl)-5,7-dihydroxy-2,2-dimethyl-6,11-dioxo-6,11-dihydro-2 H-anthra[2,3- b]pyran-8-carboxylate) and two are known compounds, emodin ( 4) and isoxanthorin ( 5). Their structures were elucidated by spectroscopic means. Crude extracts of hexane and EtOAc showed anti-plasmodial activity against the W2 strain of Plasmodium falciparum.

Anti- Pneumocystis carinii and antiplasmodial activities of primaquine-derived imidazolidin-4-ones

A series of primaquine-derived imidazolidin-4-ones were screened for their in vitro activity against Pneumocystis carinii and Plasmodium falciparum W2 strain. Most compounds were active against P. carinii above 10 μg/mL and displayed slight to marked activity. The imidazolidin-4-ones most active against P. carinii were also those most active antiplasmodial agents, in the μM range. One of the tested imidazolidin-4-ones was slightly more active than the parent primaquine and may represent a lead compound for the development of novel anti- P. carinii 8-aminoquinolines with increased stability and resistance to metabolic inactivation.

Antimalarial activity in crude extracts of some Cameroonian medicinal plants

Fifteen crude extracts from the stem bark and seeds of four medicinal plants, viz: Entandrophragma angolense, Picralima nitida, Schumanniophyton magnificum and Thomandersia hensii were tested in vitro for their antimalarial activity against the chloroquine-resistant Plasmodium falciparum W2 strain. The results showed that the extracts of these plants possessed some antimalarial activity, the methanol extract of Picralima nitida demonstrating the highest activity in vitro. Further isolation and identification of some active compounds from these plants will justify their common use in traditional medicine for the treatment of malaria or fever in Cameroon.

Anti-plasmodial Activity of Some Constituents of the Root Bark of Harungana madagascariensis LAM. (Hypericaceae)

Bazouanthrone (1), a new anthrone derivative, has been isolated from the root bark of Harungana madagascariensis, together with known compounds, feruginin A (2), harunganin (3), harunganol A (4), harunganol B (5), friedelan-3-one (6) and betulinic acid (7). The structure of the compound (1) was assigned as 3,5,8,9-tetrahydroxy-2,4,4-tri-(3,3-dimethylallyl)-6-methyl-1-(4H)-anthracenone, by means of spectroscopic analysis. The anti-plasmodial activity of the isolated compounds was evaluated in culture against W2 strain of Plasmodium falciparum. All the compounds were found to be active against the Plasmodium parasites with bazouanthrone (1) showing particular potency (IC50=1.80 microM).

Vismiaturucallone, a new Antimalarial tetracyclic triterpene from Vismia laurentii (Clusiaceae)

In the framework of our interest in antimalarial natural products from Clusiaceae family [1,2], the apolar extract of the stem bark of Vismia laurentii showed good antimalarial activity (IC50=4.6µg/ml). Thus, the isolation of its constituents led to the identification of a new tetracyclic triterpene, (20-ethylnortirucalla-7,24-dien-3-one) vismiaturucallone (1) (Fig.1) along with eight known compounds namely 3-geranyloxyemodin, vismiaquinone A (3), vismiaquinone B, bivismiaquinone, epifriedelinol, betulinic acid, tirucalla-7,24-dien-3-one, and stigmasta-7,22-dien-3-ol. Compounds (1) and (3) showed antiplasmodial activity against chloroquine-resistant W2 strain of Plasmodium falciparum with IC50 of 1.17µM and 1.42µM, respectively.

Application of multicomponent reactions to antimalarial drug discovery. Part 2: New antiplasmodial and antitrypanosomal 4-aminoquinoline γ- and δ-lactams via a ‘catch and release’ protocol

A parallel synthesis of a new series of 4-aminoquinoline γ- and δ-lactams synthesized via the Ugi 3-component 4-centre multicomponent reaction is described. The basicity of the quinoline nitrogen was exploited in the purification of compounds via a ‘catch and release’ protocol. Yields ranging from 60% to 77% and purities as high as 96% were obtained. Compound 29, the most active against a chloroquine-resistant W2 strain of Plasmodium falciparum with an IC 50 of 0.096 μM, also inhibited recombinant falcipain-2 in vitro (IC 50 = 17.6 μM). Compound 17 inhibited the growth of Trypanosoma brucei with an ED 50 of 1.44 μM whilst exhibiting a favourable therapeutic index of 409 against a human KB cell line.

Anti-plasmodial and antioxidant activities of constituents of the seed shells of Symphonia globulifera Linn f.

A xanthone derivative, named gaboxanthone ( 1), has been isolated from the seed shells of Symphonia globulifera, together with known compounds, symphonin ( 2), globuliferin ( 3), guttiferone A ( 4), sistosterol, oleanolic acid and methyl citrate. The structure of the compound was assigned as 5,10-dihydroxy-8,9-dimethoxy-2,2-dimethyl-12-(3-methylbut-2-enyl) pyrano [3,2-b]xanthen-6(2H)-one, by means of spectroscopic analysis. The anti-plasmodial and antioxidant activities of the phenolic compounds were evaluated, respectively, in culture against W2 strain of Plasmodium falciparum and using the free radical scavenging activity of the DPPH radical, respectively. Compounds 1– 4 were found to be active against the Plasmodium parasites (IC 50 of 3.53, 1.29, 3.86 and 3.17 μM, respectively). Guttiferone A ( 4) showed a potent free radical scavenging activity compared to the well-known antioxidant caffeic acid.

Synthesis and antimalarial activities of some furoxan sulfones and related furazans

Furoxan derivatives bearing a sulfone moiety at position 3 or 4 were synthesized and tested for their antimalarial action on the chloroquine-sensitive D10 and the chloroquine-resistent W2 strains of Plasmodium falciparum. The furazan analogues were considered for comparison. The most active compounds were the products in which the –SO 2R groups are at the 3-position of the furoxan system. These latter substances displayed an antimalarial activity in the μM range, possibly related in part to their ability to release NO.

Composition and anti-plasmodial activities of essential oils from some Cameroonian medicinal plants

In a search for new plant-derived biologically active compounds against malaria parasites, five essential oils extracted from the Cameroonian plants Xylopia phloiodora, Pachypodanthium confine, Antidesma laciniatum, Xylopia aethiopica, and Hexalobus crispiflorus were evaluated in regard to their anti-plasmodial activity against the W2 strain of Plasmodium falciparum. The oils were obtained from the plants with 0.12, 0.13, 0.18, 0.6 and 0.1% yields (relatively to dried material weight) respectively. Analysis by gas chromatography and mass spectrometry identified mainly terpenoids, among which α-copaene, γ-cadinene, δ-cadinene , α-cadinol, spathulenol and caryophyllene oxide were most commonly found. The five oils were active against Plasmodium falciparum in culture. The most effective was the oil of Hexalobus crispiflorus, with an IC 50 of 2 μg/ml.